Current Projects

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia: over 6 million AF patients are treated in Europe every year. Catheter ablation is a standard treatment aimed at eliminating the arrhythmogenic electrical sources (rotors) in the atria, by destroying the underlying tissue substrate with a localised radiofrequency energy delivery. However, the long-term success rates are low, with AF recurring in 30-50% of patients. This can be explained by the lack of patient-specific information on (i) the atrial wall geometry and (ii) precise locations of rotors. AF recurrence can therefore arise from (i) inadequate energy delivery and incomplete ablation and (ii) hit-and-miss outcomes of empirical ablation of "usual suspect" rotor locations. The project aims to apply novel (i) MR imaging protocols to reconstruct the atrial wall geometry from AF patients and (ii) computational models to link the atrial structure and function - and hence, to identify patient-specific locations of rotors sustaining AF. These novel tools will help improve the effectiveness of AF ablation treatment. More...

Having recently discovered a new probe to trace glycogenesis, the aim of this PhD project is to establish the biological rationale and specificity of imaging cancer-specific quiescence/senescence through measurement of enhanced glycogenesis by positron emission tomography.
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The aims of this project are to optimise the conversion of cyclotron-produced 11C-carbon monoxide to 11C-carbon dioxide using chlorosilanes as trapping and reducing agents; to use the labelled silacarboxyllic acids as alternative reagents for 11C-CO mediated carbonylation reactions; to use micro/milli-fluidic systems developed by King's and PMB to implement the efficient synthesis of compounds for in vivo PET imaging application using the developed chemistry; to use the above methods in the targeted synthesis of PET radiotracers of interest for imaging brain receptors and enzymes; to develop methods for synthesising libraries of carbon-11 compounds in order to optimise in vivo stability and binding properties. More...

This project will further develop our existing one-dimensional (1-D) model of blood flow in the arterial tree to facilitate its use for patient-specific medical planning. We will create a user-friendly workflow within the open-source Nektar++ framework (www.nektar.info) to calculate blood pressure (BP) waveforms in the larger arteries of the systemic or pulmonary circulations from patient-specific data that can be measured noninvasively in the clinic using magnetic resonance imaging. Applanation tonometry will also be used for the systemic circulation. Moreover, we will develop post-processing tools to identify the physical mechanisms underlying calculated BP waveforms by separating contributions from the heart, buffering function of the aorta or larger pulmonary arteries, and proximal and peripheral wave reflections. This project will provide a software package for rapid and accurate patient-specific BP modelling and analysis that will run on Linux, Mac and Windows platforms at a much smaller computational cost than 3-D modelling. More...

The overarching aim of the project is to develop a noninvasive biopsy system that can image the molecular signatures of a disease in its in vivo native state, in 3D, and throughout the progression of the disease. A focused ultrasound-based drug delivery system will be used to noninvasively and locally deliver normally impermeable targeted MRI contrast agents across the capillaries of a target disease (such as breast cancer). MRI pulse sequences will then be optimised to detect the bound targeted MRI contrast agents in vivo from the surrounding tissue and unbound contrast agents. The sub-aims of this project are (1) to design ultrasound parameters for delivering targeted MRI contrast agents, (2) to identify and/or design targeted MRI contrast agents that could provide sufficient signal contrast when delivered by ultrasound, and (3) to optimise MRI pulse sequences to identify bound targeted contrast agents. More...

In this project we will develop cancer cell-targeted theranostic compounds for visualizing tumours at a whole-body (using SPECT/PET) and microscopic (using optical imaging) level; at the same time the compound stabilizes guanine-rich DNA/RNA structures (G-quadruplexes) that are inhibitory to cancer cell proliferation and oncogene expression.
The probes will be built by coupling a known platinum-based cytotoxic agent (which also acts as an optical probe) and the radioisotope chelator DOTA to a peptide or antibody that selectively targets cancer cells. We will also aim to modify the platinum-based cytotoxic agent such that it is only activated in the reducing environment found within targeted cells thereby reducing potential off-target activity risks. In this way, our theranostic agent will be highly selective against cancer cells and allow tracking the tumour uptake of the cytotoxic probe on a whole-body level as well as visualize targeted cells on a microscopic level. More...

In the context of the recent arrival of simultaneous PET‐MR imaging, this project seeks to advance the field of image reconstruction for PET‐MR imaging by bringing together the progress made separately for PET and MR reconstruction, combining them into a unified PET‐MR image reconstruction framework. This will involve direct parametric reconstruction from raw PET data as well as direct parametric image reconstruction from simultaneously acquired MR k‐space data. The concept of sparsity will be exploited in both the PET and MR functional parametric map reconstructions, as a means of limiting noise, in addition to exploiting correlations between PET and MR parameters. The overall aim is to achieve a reconstruction for each modality which surpasses that obtainable from each modality in isolation. The initial focus of application will be for the imaging of brain disorders, where issues such as subject movement are easier to deal with than for imaging of the body.
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In this project techniques to increase the spatial resolution, sensitivity and image acquisition speed of super-resolved ultrasound images will be investigated. New adaptive data acquisition strategies and post-acquisition signal processing techniques will be investigated. In particular the project will investigate how recent developments in super-fast ultrasound imaging could be used to provide 3D super-resolved ultrasound imaging at resolutions far beyond the conventional diffraction limit. More...

The aim of this project is to develop novel quantitative MR techniques to characterize cardiac tissue for the management of cardiac arrhythmias. This project has a particular focus on driving the innovation that underpins an interventional MRI electrophysiology program, and these techniques can be divided into three main areas of arrhythmia management. Firstly, techniques will be developed for the assessment of the arrhythmia substrate within the atria and ventricles, guiding risk stratification and intervention planning. This will include substrate analysis for ventricular tachycardia (VT) and atrial fibrosis assessment, including fibrosis/scar quantification and wall thickness. Secondly, techniques will be developed for the live guidance of ablation procedures. Hyperacute (during radiofrequency (RF) energy delivery) and acute (within 60 min of RF delivery) techniques will include T1 mapping (3D and 2D), diffusion weighted imaging, T2 weighted imaging and gadolinium enhanced imaging (early and late). Thirdly, imaging techniques of the effect and quantification of ablation will be optimised, building upon a 3D LGE technique.
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